In Silico Investigation of Candidate Anticancer Targets for Aryltetralin Lignans Previously Reported from Cleistanthus Species
6 affiliations
- 1Faculty of Analytical Chemistry and Drug Quality Control, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi 100000, Vietnam
- 2Faculty of Pharmacy, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam
- 3Research Center for Discovery and Development of Healthcare Products, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam
- 4Department of Medicine and Pharmacy, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Hanoi 100000, Vietnam
- 5Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Hanoi 100000, Vietnam
- 6Institute of Drug Quality Control at Ho Chi Minh City, 200 Co Bac, Ho Chi Minh City 700000, Vietnam
Abstract
Aryltetralin lignans isolated from the fruits of Cleistanthus species exhibit substantial cytotoxic activity, although the molecular interactions underlying these effects remain incompletely understood. This study combined computational target investigation with previously published experimental chemical characterization and cytotoxic evidence and no new isolation or cytotoxicity experiments were carried out. Cleistantoxin, 7-hydroxypicropolygamain, neo-cleistantoxin, cleisindoside A, cleisindoside D, and cleistonkinin D were previously isolated from C. indochinensis, C. tonkinensis, C. eberhardtii and characterized by complementary spectroscopic methods. Cleistantoxin showed potent activity against MCF-7, multidrug-resistant MCF-7R, and HT29 cells, with reported IC50 values of 0.036, 0.014, and 0.035 μM, respectively. Structural similarity to podophyllotoxin-derived anticancer agents guided the investigation of DNA topoisomerase IIβ, Bcl-2, and p53 Y220C as candidate targets. Docking with AutoDock Vina-GPU 2.1 was validated by redocking the co-crystallized inhibitors (RMSD < 2 Å at the TOP2B and Bcl-2 sites; the p53 Y220C control is reported for both receptor preparations), and selected complexes were simulated in triplicate for 100 ns, followed by MM-GBSA calculations and ADMET predictions. Cleisindoside A and D kept etoposide-like hydrogen bonds to DNA in the TOP2B–DNA complex. Their MM-GBSA binding energies were −78.40 ± 3.73 and −81.90 ± 7.84 kcal·mol−1 for two ligand copies, comparable to −79.62 ± 5.14 kcal·mol−1 for etoposide. In Bcl-2, S-10r was clearly more favorable than cleisindoside D. The predicted pharmacokinetic profiles differentiated the aglycones from the glycosides and identified potential cytochrome P450 inhibition liabilities. By linking previously reported experimentally characterized natural products and cytotoxic evidence with molecular modeling, this study provides testable hypotheses for the molecular recognition of Cleistanthus lignans. Direct biochemical and mechanism-focused cellular studies are nevertheless required to validate the proposed targets.
Related
- Integrative in vitro, in vivo, and in silico investigation with mineral profiling of Combretum indicum: A multi-target therapeutic candidate exhibiting antioxidant, thrombolytic, anti-inflammatory, anti-arthritic, analgesic, cytotoxic, and anthelmintic activities
- Identification and Characterization of a Previously Uncharacterized Metagenome-Derived Chitinase and Its Application in N -Acetyl- d -Glucosamine Production from Crayfish Shell Waste
- Ribosomal RNA cleavage by the previously unidentified RelS–RelI toxin–antitoxin system controls growth of Mycobacterium tuberculosis
- In Vitro Anticancer Activity and Integrated Multi-Target Computational Analysis of Ylang-Ylang Essential Oil Against Breast Cancer
- Natural Products in Anticancer Activity: 2nd Edition—From Chemical Diversity to Mechanistic and Translational Insights
BibTeX
@article{nguyen2026silico,
title = {{In Silico Investigation of Candidate Anticancer Targets for Aryltetralin Lignans Previously Reported from Cleistanthus Species}},
author = {Lam-Hong Nguyen and Thi-Thanh-Thuy Nguyen and Dac-Nhan Nguyen and Quang-Minh Mai and Thang Le and Hai Pham-The and Van-Cuong Pham and Thi-Mai-Huong Doan and Viet-Hung Tran and Khac-Minh Thai},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203781},
url = {https://www.mdpi.com/1420-3049/31/20/3781},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - In Silico Investigation of Candidate Anticancer Targets for Aryltetralin Lignans Previously Reported from Cleistanthus Species
AU - Lam-Hong Nguyen
AU - Thi-Thanh-Thuy Nguyen
AU - Dac-Nhan Nguyen
AU - Quang-Minh Mai
AU - Thang Le
AU - Hai Pham-The
AU - Van-Cuong Pham
AU - Thi-Mai-Huong Doan
AU - Viet-Hung Tran
AU - Khac-Minh Thai
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203781
UR - https://www.mdpi.com/1420-3049/31/20/3781
AB - Aryltetralin lignans isolated from the fruits of Cleistanthus species exhibit substantial cytotoxic activity, although the molecular interactions underlying these effects remain incompletely understood. This study combined computational target investigation with previously published experimental chemical characterization and cytotoxic evidence and no new isolation or cytotoxicity experiments were carried out. Cleistantoxin, 7-hydroxypicropolygamain, neo-cleistantoxin, cleisindoside A, cleisindoside D, and cleistonkinin D were previously isolated from C. indochinensis, C. tonkinensis, C. eberhardtii and characterized by complementary spectroscopic methods. Cleistantoxin showed potent activity against MCF-7, multidrug-resistant MCF-7R, and HT29 cells, with reported IC50 values of 0.036, 0.014, and 0.035 μM, respectively. Structural similarity to podophyllotoxin-derived anticancer agents guided the investigation of DNA topoisomerase IIβ, Bcl-2, and p53 Y220C as candidate targets. Docking with AutoDock Vina-GPU 2.1 was validated by redocking the co-crystallized inhibitors (RMSD < 2 Å at the TOP2B and Bcl-2 sites; the p53 Y220C control is reported for both receptor preparations), and selected complexes were simulated in triplicate for 100 ns, followed by MM-GBSA calculations and ADMET predictions. Cleisindoside A and D kept etoposide-like hydrogen bonds to DNA in the TOP2B–DNA complex. Their MM-GBSA binding energies were −78.40 ± 3.73 and −81.90 ± 7.84 kcal·mol−1 for two ligand copies, comparable to −79.62 ± 5.14 kcal·mol−1 for etoposide. In Bcl-2, S-10r was clearly more favorable than cleisindoside D. The predicted pharmacokinetic profiles differentiated the aglycones from the glycosides and identified potential cytochrome P450 inhibition liabilities. By linking previously reported experimentally characterized natural products and cytotoxic evidence with molecular modeling, this study provides testable hypotheses for the molecular recognition of Cleistanthus lignans. Direct biochemical and mechanism-focused cellular studies are nevertheless required to validate the proposed targets.
SN - 1420-3049
ER -